Objective:Human pancreatic cancer is one of the most common clinical malignancies.The effect of comprehensive treatment based on surgery is general.The effects of chemotherapy were not obvious mainly because of lack ...Objective:Human pancreatic cancer is one of the most common clinical malignancies.The effect of comprehensive treatment based on surgery is general.The effects of chemotherapy were not obvious mainly because of lack of targeting and chemoresistance in pancreatic cancer.This study aimed to investigate the effects of folate receptor (FR)-mediated gemcitabine FA-Chi-Gem nanoparticles with a core-shell structure by electrostatic spray on pancreatic cancer.Methods:In this study,the levels of expression of FR in six human pancreatic cancer cell lines were studied by immunohistochemical analysis.The uptake rate of isothiocyanate-labeled FA-Chi nanoparticles in FR high expression cell line COLO357 was assessed by fluorescence microscope and the inhibition rate of FA-Chi-Gem nanoparticles on COLO357 cells was evaluated by MTT assay.Moreover,the biodistribution of PEG-FA-ICGDER02-Chi in the orthotopic pancreatic tumor model was observed using near-infrared imaging and the human pancreatic cancer orthotopic xenografts were treated with different nanoparticles and normal saline control.Results:The expression of FR in COLO357 was the highest among the six pancreatic cancer cell lines.The FR mainly distributed on cell membrane and fewer in the cytoplasm in pancreatic cancer.Moreover,the absorption rate of the FA-Chi-Gem nanoparticles was more than the Chi nanoparticles without FA modified.The proliferation of COLO357 was significantly inhibited by FA-Chi-Gem nanoparticles.The PEG-FA-ICGDER02-Chi nanoparticles were enriched in tumor tissue in human pancreatic cancer xenografts,while non-targeted nanoparticles were mainly in normal liver tissue.PEG-FA-Gem-Chi significantly inhibited the growth of human pancreatic cancer xenografts (PEG-FA-Gem-Chi vs.Gem,t=22.950,P=0.000).Conclusions:PEG-FA-FITC-Chi nanoparticles might be an effective targeted drug for treating human FR-positive pancreatic cancer.展开更多
Anion starch nanoparticles (StNP) were prepared in water-in-oil microemulsion. Folate modi-fied with PEG was conjugated to the surface of StNP to obtain the folate-conjugated starch nanoparticles (FA-PEG/StNP). The av...Anion starch nanoparticles (StNP) were prepared in water-in-oil microemulsion. Folate modi-fied with PEG was conjugated to the surface of StNP to obtain the folate-conjugated starch nanoparticles (FA-PEG/StNP). The average diameter of FA-PEG/ StNP determined by AFM and Zeta-Sizer apparatus was about 130 nm. Doxorubicin (DOX)-loaded FA- PEG/StNP was obtained via infiltrating combination. The result of UV spectrophotometer showed that the saturation concentration of DOX-loaded FA-PEG/ StNP was 28 μg/mg, which was effective for the con-trolled release of anticancer drug DOX. The cell ex-periments showed that the Lc50 of DOX-loaded FA-PEG/StNP and DOX-loaded StNP was higher than that of DOX, which indicates that FA-PEG/StNP and StNP can decrease the toxicity of DOX; while the lethal rate of DOX-loaded FA-PEG/StNP was 3 times that of DOX-loaded StNP with the same quantity of DOX, which indicates that FA in FA-PEG/StNP is ef-fective for improving the targeting function of nanoparticles, thus enhancing the inhibition effect of anticancer drug to cancer cell. This work demon-strates that the FA-PEG/StNP system is a potentially useful system for the targeted delivery of anticancer drug DOX.展开更多
基金supported by the National Natural Science Foundation of China(No.81071967 and 30872500)the Natural Science Foundation of Jiangsu province(Project No:BK2010242)
文摘Objective:Human pancreatic cancer is one of the most common clinical malignancies.The effect of comprehensive treatment based on surgery is general.The effects of chemotherapy were not obvious mainly because of lack of targeting and chemoresistance in pancreatic cancer.This study aimed to investigate the effects of folate receptor (FR)-mediated gemcitabine FA-Chi-Gem nanoparticles with a core-shell structure by electrostatic spray on pancreatic cancer.Methods:In this study,the levels of expression of FR in six human pancreatic cancer cell lines were studied by immunohistochemical analysis.The uptake rate of isothiocyanate-labeled FA-Chi nanoparticles in FR high expression cell line COLO357 was assessed by fluorescence microscope and the inhibition rate of FA-Chi-Gem nanoparticles on COLO357 cells was evaluated by MTT assay.Moreover,the biodistribution of PEG-FA-ICGDER02-Chi in the orthotopic pancreatic tumor model was observed using near-infrared imaging and the human pancreatic cancer orthotopic xenografts were treated with different nanoparticles and normal saline control.Results:The expression of FR in COLO357 was the highest among the six pancreatic cancer cell lines.The FR mainly distributed on cell membrane and fewer in the cytoplasm in pancreatic cancer.Moreover,the absorption rate of the FA-Chi-Gem nanoparticles was more than the Chi nanoparticles without FA modified.The proliferation of COLO357 was significantly inhibited by FA-Chi-Gem nanoparticles.The PEG-FA-ICGDER02-Chi nanoparticles were enriched in tumor tissue in human pancreatic cancer xenografts,while non-targeted nanoparticles were mainly in normal liver tissue.PEG-FA-Gem-Chi significantly inhibited the growth of human pancreatic cancer xenografts (PEG-FA-Gem-Chi vs.Gem,t=22.950,P=0.000).Conclusions:PEG-FA-FITC-Chi nanoparticles might be an effective targeted drug for treating human FR-positive pancreatic cancer.
文摘Anion starch nanoparticles (StNP) were prepared in water-in-oil microemulsion. Folate modi-fied with PEG was conjugated to the surface of StNP to obtain the folate-conjugated starch nanoparticles (FA-PEG/StNP). The average diameter of FA-PEG/ StNP determined by AFM and Zeta-Sizer apparatus was about 130 nm. Doxorubicin (DOX)-loaded FA- PEG/StNP was obtained via infiltrating combination. The result of UV spectrophotometer showed that the saturation concentration of DOX-loaded FA-PEG/ StNP was 28 μg/mg, which was effective for the con-trolled release of anticancer drug DOX. The cell ex-periments showed that the Lc50 of DOX-loaded FA-PEG/StNP and DOX-loaded StNP was higher than that of DOX, which indicates that FA-PEG/StNP and StNP can decrease the toxicity of DOX; while the lethal rate of DOX-loaded FA-PEG/StNP was 3 times that of DOX-loaded StNP with the same quantity of DOX, which indicates that FA in FA-PEG/StNP is ef-fective for improving the targeting function of nanoparticles, thus enhancing the inhibition effect of anticancer drug to cancer cell. This work demon-strates that the FA-PEG/StNP system is a potentially useful system for the targeted delivery of anticancer drug DOX.